scholarly journals Rescuing Immunosenescence via Non-Specific Vaccination

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 231-239
Author(s):  
Alexander I. Mosa
Keyword(s):  
Immune Responses ◽  
The Elderly ◽  
Short Review ◽  
Functional Markers ◽  
Healthy Life ◽  
Related Disease ◽  
Age Related ◽  
Population Vulnerability ◽  
Mechanistic Basis ◽  
Promising Avenue

Discrepancies in lifespan and healthy-life span are predisposing populations to an increasing burden of age-related disease. Accumulating evidence implicates aging of the immune system, termed immunosenescence, in the pathogenesis of multiple age-related diseases. Moreover, immune dysregulation in the elderly increases vulnerability to infection and dampens pathogen-specific immune responses following vaccination. The health challenges manifesting from these age related deficits have been dramatically exemplified by the current SARS-CoV-2 pandemic. Approaches to either attenuate or reverse functional markers of immunosenescence are therefore urgently needed. Recent evidence suggests systemic immunomodulation via non-specific vaccination with live-attenuated vaccines may be a promising avenue to at least reduce aged population vulnerability to viral infection. This short review describes current understanding of immunosenescence, the historical and mechanistic basis of vaccine-mediated immunomodulation, and the outstanding questions and challenges required for broad adoption.

Inherited glaucoma in DBA/2J mice: Pertinent disease features for studying the neurodegeneration

2005 ◽  
Vol 22 (5) ◽  
pp. 637-648 ◽  
Author(s):  
RICHARD T. LIBBY ◽  
MICHAEL G. ANDERSON ◽  
IOK-HOU PANG ◽  
ZACHARY H. ROBINSON ◽  
OLGA V. SAVINOVA ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cells ◽  
The Elderly ◽  
Nerve Degeneration ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Future Studies ◽  
Age Related ◽  
Iop Elevation ◽  
Mechanistic Basis

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8–9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.

scholarly journals Chronic Inflammation as an Immunological Abnormality and Effectiveness of Exercise

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 223 ◽  
Author(s):  
Katsuhiko Suzuki
Keyword(s):  
Chronic Inflammation ◽  
Pathological Condition ◽  
Inflammatory Cells ◽  
The Elderly ◽  
Healthy Life ◽  
Daily Lives ◽  
Food Ingredients ◽  
Tissue Degeneration ◽  
Age Related

Reduced levels of physical activity in people’s daily lives cause the development of metabolic syndromes or age-related disorders. Chronic inflammation is now understood to be an underlying pathological condition in which inflammatory cells such as neutrophils and monocyte/macrophages infiltrate into fat and other tissues and accumulate when people become obese due to overeating and/or physical inactivity. Pro-inflammatory mediators such as cytokines that are secreted in excess from inflammatory cells will not only lead to the development of arteriosclerosis when they chronically affect blood vessels but also bring tissue degeneration and/or dysfunction to various organs. Chronic inflammation is also involved in sarcopenia that brings hypofunction in the elderly, dementia, osteoporosis, or cancer and negatively affects many chronic diseases and people’s healthy life expectancy. In this paper, outlines of such studies are introduced in terms of homeostatic inflammation, which occurs chronically due to the innate immune system and its abnormalities, while focusing on the efficacy of exercise from aspects of immunology and oxidative stress. The preventative effects of functional food ingredients in combination with exercise are also introduced and described. The challenges and future directions in understanding the role of exercise in the control of chronic inflammation are discussed.

scholarly journals Pathogenesis of Influenza A(H7N9) Virus in Aged Nonhuman Primates

2020 ◽  
Vol 222 (7) ◽  
pp. 1155-1164 ◽  
Author(s):  
Satoshi Fukuyama ◽  
Kiyoko Iwatsuki-Horimoto ◽  
Maki Kiso ◽  
Noriko Nakajima ◽  
Robert W Gregg ◽  
...  
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Influenza A ◽  
Nonhuman Primates ◽  
The Elderly ◽  
Mortality Rates ◽  
H7n9 Virus ◽  
Aged Animal ◽  
Chemokine Production ◽  
Mechanistic Basis

Abstract The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20–26 years) caused more severe symptoms than infection of young animals (defined as age 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus.

scholarly journals New Horizons: Novel Approaches to Enhance Healthspan Through Targeting Cellular Senescence and Related Aging Mechanisms

2020 ◽  
Author(s):  
Tamar Tchkonia ◽  
Allyson K Palmer ◽  
James L Kirkland
Keyword(s):  
Cellular Senescence ◽  
The Elderly ◽  
Protein Accumulation ◽  
Unitary Theory ◽  
Research Attention ◽  
New Horizons ◽  
Related Disease ◽  
Age Related ◽  
Metabolite Generation ◽  
Aging Mechanisms

Abstract The elderly population is increasing faster than other segments of the population throughout the world. Age is the leading predictor for most chronic diseases and disorders, multimorbidity, geriatric syndromes, and impaired ability to recover from accidents or illnesses. Enhancing the duration of health and independence, termed healthspan, would be more desirable than extending lifespan merely by prolonging the period of morbidity toward the end of life. The geroscience hypothesis posits that healthspan can be extended by targeting fundamental aging mechanisms, rather than attempting to address each age-related disease one at a time, only so the afflicted individual survives disabled and dies shortly afterward of another age-related disease. These fundamental aging mechanisms include, among others, chronic inflammation, fibrosis, stem cell/ progenitor dysfunction, DNA damage, epigenetic changes, metabolic shifts, destructive metabolite generation, mitochondrial dysfunction, misfolded or aggregated protein accumulation, and cellular senescence. These processes appear to be tightly interlinked, as targeting any one appears to affect many of the rest, underlying our Unitary Theory of Fundamental Aging Mechanisms. Interventions targeting many fundamental aging processes are being developed, including dietary manipulations, metformin, mTOR (mechanistic target of rapamycin) inhibitors, and senolytics, which are in early human trials. These interventions could lead to greater healthspan benefits than treating age-related diseases one at a time. To illustrate these points, we focus on cellular senescence and therapies in development to target senescent cells. Combining interventions targeting aging mechanisms with disease-specific drugs could result in more than additive benefits for currently difficult-to-treat or intractable diseases. More research attention needs to be devoted to targeting fundamental aging processes.

Pathogenesis and clinical implications of HIV-related anemia in 2013

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 377-381 ◽  
Author(s):  
Amanda J. Redig ◽  
Nancy Berliner
Keyword(s):  
Antiretroviral Therapy ◽  
Accelerated Aging ◽  
The Elderly ◽  
Chronic Obstructive ◽  
Combination Antiretroviral Therapy ◽  
Obstructive Pulmonary Disease ◽  
Related Disease ◽  
Age Related ◽  
Entry Points ◽  
The Face

AbstractAnemia is a common feature of HIV-related disease and has been uniformly demonstrated to be an independent predictor of morbidity and mortality. Although anemia often responds to combination antiretroviral therapy, many patients remain anemic despite therapy and such persistent anemia continues to negatively affect prognosis regardless of drug response. Anemia is also a common feature of normal aging. We postulate that the pathophysiology of anemia in HIV, especially that which persists in the face of combination antiretroviral therapy, is a reflection of underlying proinflammatory pathways that are also thought to contribute to anemia in the elderly, as well as other age-related chronic diseases such as cardiovascular disease and chronic obstructive pulmonary disease. This suggests that HIV induces inflammatory pathways that are associated with a pattern of accelerated aging and that anemia is a biomarker of these processes. A better understanding of the pathophysiology of HIV-related anemia may provide important entry points for improving the chronic manifestations of HIV-related disease.

scholarly journals Serum but not mucosal antibody responses are predicted by pre-existing SARS-CoV-2 spike cross-reactive CD4+ T cells following BNT162b2 vaccination in the elderly

2021 ◽  
Author(s):  
Lil Meyer-Arndt ◽  
Tatjana Schwarz ◽  
Lucie Loyal ◽  
Larissa Henze ◽  
Beate Kruse ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Natural Infection ◽  
The Elderly ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Mucosal Antibody ◽  
Age Related ◽  
Neutralizing Capacity ◽  
Efficient Induction

AbstractAdvanced age is a main risk factor for severe COVID-19 and thus elderly were often prioritized for vaccination. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analysed cellular, serological and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to BNT162b2 COVID-19 vaccine in old (69-92 years) and middle-aged (24-57 years) vaccinees compared to natural infection (COVID-19 convalescents of 21-55 years). Serological humoral responses to vaccination exceeded those of convalescents but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+ T cells correlated with efficient induction of serological anti-S1 IgG and neutralizing capacity after vaccination. Our results highlight the role of pre-existing cross-reactive CD4+ T cells with respect to SARS-CoV-2 vaccination particularly in old individuals, in whom their presence predicted efficient COVID-19-vaccine-induced humoral immune responses.

scholarly journals Assessment of Lymph Node Stromal Cells as an Underlying Factor in Age-Related Immune Impairment

2019 ◽  
Vol 74 (11) ◽  
pp. 1734-1743 ◽  
Author(s):  
April R Masters ◽  
Alexxus Hall ◽  
Jenna M Bartley ◽  
Spencer R Keilich ◽  
Erica C Lorenzo ◽  
...  
Keyword(s):  
T Cells ◽  
Steady State ◽  
Immune Responses ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Influenza Infection ◽  
Cell Subset ◽  
The Elderly ◽  
Age Related ◽  
The Impact

Abstract Aging negatively impacts immunity, resulting in inefficient responses to vaccinations and infections. Fibroblastic reticular cells (FRCs) are the major stromal cell subset in lymph nodes (LNs) and play an intricate role in the orchestration and control of adaptive immune responses. Although stromal cells have a major impact on immune responses, the impact of aging on LN stromal cells remains unclear. Quantitative analysis of LN stromal cells by flow cytometry revealed that there are no significant differences in the number of stromal cells in young and aged LN at steady state but after influenza infection aged FRCs have delayed expansion as a result of reduced proliferation. Aged LNs also produce reduced levels of homeostatic chemokines, which correlates with reduced homing of naive T cells. Image analysis reveals that young and aged T-cell zone FRCs have similar morphology at steady state and after infection. Furthermore, aged FRCs did not appear to be a contributing factor in the reduced proliferation of young T cells transferred into aged LNs after influenza infection. These results demonstrate that aging alters LN stromal cell response to challenge and these age-related changes may be an underlying contributor to impaired immune responses in the elderly people.

scholarly journals Age-Related Impairment of Innate and Adaptive Immune Responses Following Intranasal Herpes Simplex Infection

2022 ◽  
Author(s):  
Ruchi Srivastava ◽  
Anshu Agrawal ◽  
Hawa Vahed ◽  
Lbachir BenMohamed
Keyword(s):  
Immune Response ◽  
Herpes Simplex ◽  
Immune Responses ◽  
The Elderly ◽  
Adaptive Immune Responses ◽  
Herpes Infection ◽  
Aged Mice ◽  
Adaptive Immune ◽  
Age Related ◽  
Hsv 1

Immune function declines with age, leading to an increased vulnerability to respiratory viral infections. The mechanisms by which aging negatively impacts the innate and adaptive immune system leading to enhanced susceptibility to infections remain to be fully elucidated. In the present study, we used a mouse model of intranasal infection with herpes simplex virus type 1 (HSV-1), a virus that can enter the lungs through the nasal route causing pneumonia, a serious health concern in the elderly. Following intranasal inoculation of young (6 weeks), adult (36 weeks), and aged (68 weeks) with HSV-1 (KOS strain) we: (i) compared the local and systemic innate and adaptive immune response to infection; and (ii) correlated the level and type of immune response to protection against HSV-1 infection. Compared to young and adult mice, aged mice displayed: (i) increased basal level activation of epithelial cells with a decreased expression of TLR3; (ii) increased activation of dendritic cells with increased expression of MHC-1, MHC-II and CD80/86; and (iii) decreased production of type-I interferons upon stimulation; (iv) a delay in cytokines and chemokines production in the lungs; and (v) an impairment in function (CD107 and IFN-g production) of HSV-specific CD8+ T cells. These impairment in innate and adaptive immune responses in aged mice following intranasal HSV-1 inoculation was associated with symptomatic herpes infection. The findings suggest an age-related impairment of both innate and adaptive immune responses which may exacerbate herpes infection and disease in the elderly.

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